Therapeutic potential of lorlatinib in ALK-mutated metastatic paraganglioma: Insights from clinical case report and literature review.
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Paragangliomas (PGLs) are rare neuroendocrine tumours that may display metastatic potential and have limited treatment options once advanced. The aim of this paper was to review the literature data available on the treatment of metastatic PGL, focusing on targeted therapy with anaplastic lymphoma kinase (ALK) inhibitor. In this scenario, we report a case of a 16-year-old boy with metastatic PGL, initially presenting back pain and substantial disease involvement in the thoracic spine, abdominal organs, and skeletal system. After failure of standard treatments, molecular profiling was conducted on tumour samples. The presence of a pathogenic ALK point mutation, specifically F1174L, led to off-label therapy with the ALK inhibitor lorlatinib. After starting treatment, the patient experienced rapid overall improvement, including complete resolution of pain, decreased plasma catecholamine levels, and stabilization of disease, with excellent treatment tolerance. After 12 months of therapy, imaging revealed reduced tumour burden, particularly in the thoraco-lumbar region. This case represents the first report of a PGL harbouring ALK F1174L mutation, successfully treated with lorlatinib. It underscores the utility of molecular profiling in rare cancers and the potential for targeted therapy to provide durable responses and improve outcomes where traditional treatments fail. As literature on the treatment of metastatic PGL is poor and largely based on retrospective studies, case series and case reports, and few clinical trials are available, our experience contributes valuable clinical insight and suggests that genetic testing and personalized treatment strategies, including ALK inhibitors, may offer new hope for patients with metastatic PGLs.